tbuckley/cabot-search huggingface dataset:
Perspectives on acute myeloid leukemia diagnosis: a comparative analysis of the latest World Health Organization and the International Consensus Classifications
Authors: Jin Jung, Daehun Kwag, Yonggoo Kim, Jong-Mi Lee, Ari Ahn, Hoon Seok Kim, Byunggyu Bae, Silvia Park, Hee-Je Kim, Byung-Sik Cho, Myungshin Kim
Journal: Leukemia (2023)

Recently, the 5th edition of 'The World Health Organization (WHO) Classification of Tumors of Haematopoietic and Lymphoid Tissues' (WHO2022) was released in beta version [1].In WHO2022, the classification of AML underwent changes, separating AML with defining genetic abnormalities from AML defined by differentiation (AML-Diff).Additionally, AML with myelodysplasia-related changes (AML-MRC) was renamed 'AML myelodysplasia-related' (AML-MR), with updates including the removal of morphology as a sole diagnostic premise, revised cytogenetic criteria, and a mutation-based definition.An independent proposal, the International Consensus Classification (ICC), was also published during the same period [2].This study aims to compare and analyze these two classifications, focusing on AML's diagnostic criteria and entity definition. METHODS PatientsA total of 861 newly-diagnosed AML patients aged ≥18 years, according to the revised 4th WHO classification (WHO2016) [3], were included from Oct. 2017 and Oct. 2021 at Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (Fig. 1A).Bone marrow samples were independently reviewed and re-classified by five experienced haematopathologists (JJ, YK, J-ML, AA and MK).Risk stratification followed the 2022 European LeukemiaNet (ELN) classification [4].The study's last follow-up was Dec. 22nd, 2022 for survivors.Institutional Review Board approval was obtained (IRB No: KC23RISI0243).Chi-square, Fisher's exact, Mann-Whitney U, and Kruskal-Wallis H tests were used for comparison.Kaplan-Meier analysis with log-rank test was applied to plot overall survival (OS) curves.Prism version 9.5.
Correction: Reprogramming anchorage dependency by adherent‑to‑suspension transition promotes metastatic dissemination
Authors: Hyunbin D. Huh, Yujin Sub, Jongwook Oh, Ye Eun Kim, Ju Young Lee, Hwa‑Ryeon Kim, Soyeon Lee, Hannah Lee, Sehyung Pak, Sebastian E. Amos, Danielle Vahala, Jae Hyung Park, Ji Eun Shin, So Yeon Park, Han Sang Kim, Young Hoon Roh, Han‑Woong Lee, Kun‑Liang Guan, Yu Suk Choi, Joon Jeong, Junjeong Choi, Jae‑Seok Roe, Heon Yung Gee, Hyun Woo Park
Journal: Molecular Cancer (2023)

Bioinformatics of published human cell line RNA-seq data analysesRNA-seq fastq files were obtained from the ENCODE database.CLC Genomics Workbench 9.5.3 software (Qiagen, Germany) was used to map the reads to the human genome (hg19, build name GRCh37) and to generate gene expression values in the form of normalized transcripts per kilobase million (nTPM).Microarray data were obtained from the Human Protein Atlas (HPA) database in the form of matrices (row -official gene symbol, column -cell line) that included transcripts per million (TPM) values.Each of these data sets were imported into R for further analysis.Then, the data from the HPA were quantile normalized.R v3.6.3 was used to perform principal components and correlation analyses.Hierarchical clustering of these data was performed with the R package Pheatmap (version1.0.12).All cell lines were grouped into adhesion cells verus suspension cells based on their known morphology and anchorage dependency.Differentially expressed genes (DEGs) were selected based on absolute fold changes > 2, absolute Molecular Cancer
NAD+ salvage governs the immunosuppressive capacity of mesenchymal stem cells
Authors: Jiankai Fang, Pengbo Hou, Shisong Liu, Muqiu Zuo, Zhanhong Liu, Wangwang Chen, Yuyi Han, Yanan Li, Tingting Wang, Chao Feng, Peishan Li, Changshun Shao, Yufang Shi
Journal: Cellular and Molecular Immunology (2023)
Impact of primary to secondary care data sharing on care quality in NHS England hospitals
Authors: Joe Zhang, Hutan Ashrafian, Brendan Delaney, Ara Darzi
Journal: npj Digital Medicine (2023)

Abstract Health information exchange (HIE) is seen as a key component of effective care but remains poorly evidenced at a health system level. In the UK National Health Service (NHS), the ability to share primary care data with secondary care clinicians is a focus of continued digital investment. In this study, we report the evolution of interoperable technology across a period of rapid digital transformation in NHS England from 2015 to 2019, and test association of primary to secondary care data-sharing capabilities with clinical care quality indicators across all acute secondary care providers ( n = 135 NHS Trusts). In multivariable analyses, data-sharing capabilities are associated with reduction in patients breaching an Accident &amp; Emergency (A&amp;E) 4-h decision time threshold, and better patient-reported experience of acute hospital care quality. Using synthetic control analyses, we estimate mean 2.271% (STD+/−3.371) absolute reduction in A&amp;E 4-h decision time breach, 12 months following introduction of data-sharing capabilities. Our findings support current digital transformation programmes for developing regional HIE networks but highlight the need to focus on implementation factors in addition to technological procurement.
Challenging and understanding gendered narratives: the development and validation of the transnormativity measure (TM)
Authors: Louis Lindley, Stephanie L. Budge
Journal: International Journal of Transgender Health (2023)

AbstractBackground: Transnormativity refers to the accountability structure that regulates the acceptable gender presentations, narratives, and ways of being of trans and nonbinary (TNB) individuals.Aims: The present research extends prior qualitative research on transnormativity to develop and validate the Transnormativity Measure (TM).Methods: The initial developed pool of potential items was presented to a focus groups and three content experts for review. In Study 1 (N = 497), the 69 initial items of the TM hypothesized to underly a six-factor structure were analyzed using Exploratory Factor Analysis (EFA) and construct and discriminant validity were assessed. In Study 2 (N = 540), an independent sample of TNB participants' TM responses were subjected to Confirmatory Factor Analysis (CFA), invariance testing, and construct and predictive validity. Finally, in Study 3 (N = 107), an Interclass Correlation Coefficients 2-way mixed-effects model of the TM was assessed.Results: EFAs conducted in Study 1 revealed a two-factor structure as the best fit with 50 items removed. Conceptually there was considerable overlap in the items comprising the two factors and it was decided that one general factor should be utilized. Study 1 also provided preliminary construct and discriminant validity due to expected relations between the TM and existing measures of heteronormativity and internalized transphobia. In Study 2 findings from correlational tests of the remaining items revealed that four items were highly correlated and were removed. Subsequent CFA indicated that the one factor model fit the data well. Configural invariance was supported however metric noninvariance was found. Additionally, Study 2 results supported construct and predictive validity through correlations between the TM and measures of TNB community belonginess and mental health outcomes. Finally, Study 3 provided support for test-retest reliability.Discussion: Across three studies, the TM was found to be a valid measure of transnormativity.Keywords: Cisnormativityheteronormativitymeasure developmentmental health outcomestrans and nonbinarytransnormativity AcknowledgementThe authors would like to thank Dr. Austin Johnson, Dr. Paz Galupo, and Nova Bradford for their detailed reviews of the proposed items of the TM.Disclosure statementNo potential conflict of interest was reported by the authors.Role of funding sourcesThis research received funding from the Baldwin Wisconsin Idea Endowment at the University of Wisconsin-Madison.Conflicts of interest/competing interestThe authors have no conflicts of interest nor competing interests to report.Availability of data and materialThe authors have not deposited the data in a publicly accessible database.Code availabilityNot applicable.
Author Correction: Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma
Authors: Renáta Váraljai, Lisa Zimmer, Yahya Al-Matary, Paulien Kaptein, Lea J. Albrecht, Batool Shannan, Jan C. Brase, Daniel Gusenleitner, Teresa Amaral, Nina Wyss, Jochen Utikal, Lukas Flatz, Florian Rambow, Hans Christian Reinhardt, Jenny Dick, Daniel R. Engel, Susanne Horn, Selma Ugurel, Wiebke Sondermann, Elisabeth Livingstone, Antje Sucker, Annette Paschen, Fang Zhao, Jan M. Placke, Jasmin M. Klose, Wolfgang P. Fendler, Daniela S. Thommen, Iris Helfrich, Dirk Schadendorf, Alexander Roesch
Journal: Nature Cancer (2023)

In the version of this article initially published, the description of the proteomic analysis was incorrectly termed reverse phase protein array (RPPA) instead of liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).The Figure 3d schematic and Figure 3d,e legends as well as the Extended Data Figure 3 legend have been updated, and the Results section "The IL-17-associated cellular microenvironment in dual ICI" and Methods section "In vivo studies" have been corrected accordingly.The error does not affect the results or conclusions of this article, and we apologize for any confusion this may have caused.
Correctional policies for the management of trans people in Australian prisons
Authors: Charlie Winter
Journal: International Journal of Transgender Health (2023)

Background: Despite existing international standards for the prison management of incarcerated trans people, carceral policies across Australian jurisdictions vary in their availability, breadth, and appropriateness. Trans populations in prison represent a vulnerable population, having specific needs surrounding their health, safety, and wellbeing. Prior reviews into Australian carceral policies highlight where contemporary prison practices fall short of meeting those specific needs.Aims/method: A review was conducted on the available carceral policy documents of each Australian correctional service regime, examining their coverage of issues including healthcare access, placement decisions, and classification systems against international standards and prior Australian recommendations. Forty-one relevant policy documents were reviewed against eighteen benchmark recommendations, along with supplementary data.Results: Australian jurisdictions varied widely on the coverage of the reviewed areas. Benchmark attainment ranged from twelve out of eighteen (Victoria and Western Australia) to three out of eighteen (Queensland). The use of administrative segregation was identified as the area in most need of policy reform. No jurisdiction met every benchmark.Conclusions: This review highlights the need for carceral policy reform across Australian jurisdictions in order to meet the unique needs of incarcerated trans people, especially in the areas of administrative segregation and healthcare access. The review also highlights the need for carceral policy reform to bring Australian jurisdictions in line with each other on the management of incarcerated trans people, to reduce disparate outcomes across states and territories.
Current views on meningeal lymphatics and immunity in aging and Alzheimer’s disease
Authors: Shanon Rego, Guadalupe Sanchez, Sandro Da Mesquita
Journal: Molecular Neurodegeneration (2023)

Abstract Alzheimer’s disease (AD) is an aging-related form of dementia associated with the accumulation of pathological aggregates of amyloid beta and neurofibrillary tangles in the brain. These phenomena are accompanied by exacerbated inflammation and marked neuronal loss, which altogether contribute to accelerated cognitive decline. The multifactorial nature of AD, allied to our still limited knowledge of its etiology and pathophysiology, have lessened our capacity to develop effective treatments for AD patients. Over the last few decades, genome wide association studies and biomarker development, alongside mechanistic experiments involving animal models, have identified different immune components that play key roles in the modulation of brain pathology in AD, affecting its progression and severity. As we will relay in this review, much of the recent efforts have been directed to better understanding the role of brain innate immunity, and particularly of microglia. However, and despite the lack of diversity within brain resident immune cells, the brain border tissues, especially the meninges, harbour a considerable number of different types and subtypes of adaptive and innate immune cells. Alongside microglia, which have taken the centre stage as important players in AD research, there is new and exciting evidence pointing to adaptive immune cells, namely T and B cells found in the brain and its meninges, as important modulators of neuroinflammation and neuronal (dys)function in AD. Importantly, a genuine and functional lymphatic vascular network is present around the brain in the outermost meningeal layer, the dura. The meningeal lymphatics are directly connected to the peripheral lymphatic system in different mammalian species, including humans, and play a crucial role in preserving a “healthy” immune surveillance of the CNS, by shaping immune responses, not only locally at the meninges, but also at the level of the brain tissue. In this review, we will provide a comprehensive view on our current knowledge about the meningeal lymphatic vasculature, emphasizing its described roles in modulating CNS fluid and macromolecule drainage, meningeal and brain immunity, as well as glial and neuronal function in aging and in AD.
Development and validation of a reinforcement learning model for ventilation control during emergence from general anesthesia
Authors: Hyeonhoon Lee, Hyun-Kyu Yoon, Jaewon Kim, Ji Soo Park, Chang-Hoon Koo, Dongwook Won, Hyung-Chul Lee
Journal: npj Digital Medicine (2023)

Ventilation should be assisted without asynchrony or cardiorespiratory instability during anesthesia emergence until sufficient spontaneous ventilation is recovered. In this multicenter cohort study, we develop and validate a reinforcement learning-based Artificial Intelligence model for Ventilation control during Emergence (AIVE) from general anesthesia. Ventilatory and hemodynamic parameters from 14,306 surgical cases at an academic hospital between 2016 and 2019 are used for training and internal testing of the model. The model's performance is also evaluated on the external validation cohort, which includes 406 cases from another academic hospital in 2022. The estimated reward of the model's policy is higher than that of the clinicians' policy in the internal (0.185, the 95% lower bound for best AIVE policy vs. -0.406, the 95% upper bound for clinicians' policy) and external validation (0.506, the 95% lower bound for best AIVE policy vs. 0.154, the 95% upper bound for clinicians' policy). Cardiorespiratory instability is minimized as the clinicians' ventilation matches the model's ventilation. Regarding feature importance, airway pressure is the most critical factor for ventilation control. In conclusion, the AIVE model achieves higher estimated rewards with fewer complications than clinicians' ventilation control policy during anesthesia emergence.
GDNF gene therapy for alcohol use disorder in male non-human primates
Authors: Matthew M. Ford, Brianna E. George, Victor S. Van Laar, Katherine M. Holleran, Jerusha Naidoo, Piotr Hadaczek, Lauren E. Vanderhooft, Emily G. Peck, Monica H. Dawes, Kousaku Ohno, John Bringas, Jodi L. McBride, Lluis Samaranch, John R. Forsayeth, Sara R. Jones, Kathleen A. Grant, Krystof S. Bankiewicz
Journal: Nature Medicine (2023)
Short-term dietary changes can result in mucosal and systemic immune depression
Authors: Francesco Siracusa, Nicola Schaltenberg, Yogesh Kumar, Till R. Lesker, Babett Steglich, Timur Liwinski, Filippo Cortesi, Laura Frommann, Björn-Phillip Diercks, Friedericke Bönisch, Alexander W. Fischer, Pasquale Scognamiglio, Mira J. Pauly, Christian Casar, Yotam Cohen, Penelope Pelczar, Theodora Agalioti, Flemming Delfs, Anna Worthmann, Ramez Wahib, Bettina Jagemann, Hans-Willi Mittrücker, Oliver Kretz, Andreas H. Guse, Jakob R. Izbicki, Kara G. Lassen, Till Strowig, Michaela Schweizer, Eduardo J. Villablanca, Eran Elinav, Samuel Huber, Joerg Heeren, Nicola Gagliani
Journal: Nature Immunology (2023)

Abstract Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences of this short-term consumption of energy-dense nutrients are unclear. Here, we show that short-term reiterative switching to ‘feast diets’, mimicking our social eating behavior, breaches the potential buffering effect of the intestinal microbiota and reorganizes the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic immunity, leading to higher susceptibility to Salmonella enterica serovar Typhimurium and Listeria monocytogenes infections. The ability to respond to antigenic challenges with a model antigen was also impaired. These observations could be explained by a reduction of CD4 + T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to reduced microbial provision of fiber metabolites. Reintroducing dietary fiber rewired T cell metabolism and restored mucosal and systemic CD4 + T cell functions and immunity. Finally, dietary intervention with human volunteers confirmed the effect of short-term dietary switches on human CD4 + T cell functionality. Therefore, short-term nutritional changes cause a transient depression of mucosal and systemic immunity, creating a window of opportunity for pathogenic infection.
Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial
Authors: Kenneth B. Baker, Ela B. Plow, Sean Nagel, Anson B. Rosenfeldt, Raghavan Gopalakrishnan, Cynthia Clark, Alexandria Wyant, Madeleine Schroedel, John Ozinga, Sara Davidson, Olivia Hogue, Darlene Floden, Jacqueline Chen, Paul J. Ford, Lauren Sankary, Xuemei Huang, David A. Cunningham, Frank P. DiFilippo, Bo Hu, Stephen E. Jones, Francois Bethoux, Steven L. Wolf, John Chae, André G. Machado
Journal: Nature Medicine (2023)

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1-3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443 .
In vivo screening characterizes chromatin factor functions during normal and malignant hematopoiesis
Authors: David Lara-Astiaso, Ainhoa Goñi-Salaverri, Julen Mendieta-Esteban, Nisha Narayan, Cynthia Del Valle, Torsten Gross, George Giotopoulos, Tumas Beinortas, Mar Navarro-Alonso, Laura Pilar Aguado-Alvaro, Jon Zazpe, Francesco Marchese, Natalia Torrea, Isabel A. Calvo, Cecile K. Lopez, Diego Alignani, Aitziber Lopez, Borja Saez, Jake P. Taylor-King, Felipe Prosper, Nikolaus Fortelny, Brian J. P. Huntly
Journal: Nature Genetics (2023)

Abstract Cellular differentiation requires extensive alterations in chromatin structure and function, which is elicited by the coordinated action of chromatin and transcription factors. By contrast with transcription factors, the roles of chromatin factors in differentiation have not been systematically characterized. Here, we combine bulk ex vivo and single-cell in vivo CRISPR screens to characterize the role of chromatin factor families in hematopoiesis. We uncover marked lineage specificities for 142 chromatin factors, revealing functional diversity among related chromatin factors (i.e. barrier-to-autointegration factor subcomplexes) as well as shared roles for unrelated repressive complexes that restrain excessive myeloid differentiation. Using epigenetic profiling, we identify functional interactions between lineage-determining transcription factors and several chromatin factors that explain their lineage dependencies. Studying chromatin factor functions in leukemia, we show that leukemia cells engage homeostatic chromatin factor functions to block differentiation, generating specific chromatin factor–transcription factor interactions that might be therapeutically targeted. Together, our work elucidates the lineage-determining properties of chromatin factors across normal and malignant hematopoiesis.
Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity
Authors: Lucy C. Garner, Ali Amini, Michael E. B. FitzPatrick, Martin J. Lett, Gabriel F. Hess, Magdalena Filipowicz Sinnreich, Nicholas M. Provine, Paul Klenerman
Journal: Nature Immunology (2023)

Abstract Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA-sequencing, a method to integrate function and TCR clonotype at single-cell resolution. MAIT cell clonal diversity was comparable to conventional memory T cells, with private TCR repertoires shared across matched tissues. Baseline functional diversity was low and largely related to tissue site. MAIT cells showed stimulus-specific transcriptional responses in vitro, with cells positioned along gradients of activation. Clonal identity influenced resting and activated transcriptional profiles but intriguingly was not associated with the capacity to produce IL-17. Overall, MAIT cells show phenotypic and functional diversity according to tissue localization, stimulation environment and clonotype.
Single-cell multiomic analysis of thymocyte development reveals drivers of CD4+ T cell and CD8+ T cell lineage commitment
Authors: Zoë Steier, Dominik A. Aylard, Laura L. McIntyre, Isabel Baldwin, Esther Jeong Yoon Kim, Lydia K. Lutes, Can Ergen, Tse-Shun Huang, Ellen A. Robey, Nir Yosef, Aaron Streets
Journal: Nature Immunology (2023)

The development of CD4
Equitable hiring strategies towards a diversified faculty
Authors: Elizabeth M. Cosgriff-Hernandez, Brian A. Aguado, Belinda Akpa, Gabriella Coloyan Fleming, Erika Moore, Ana Maria Porras, Patrick M. Boyle, Deva D. Chan, Naomi Chesler, Karen L. Christman, Tejal A. Desai, Brendan A. C. Harley, Gregory A. Hudalla, Megan L. Killian, Katharina Maisel, Kristen C. Maitland, Shelly R. Peyton, Beth L. Pruitt, Sarah E. Stabenfeldt, Kelly R. Stevens, Audrey K. Bowden
Journal: Nature Biomedical Engineering (2023)